Comparative efficacy of clarithromycin modified-release and clarithromycinimmediate-release formulations in the treatment of lower respiratory tractinfection

Background: A modified-release (MR) formulation of clarithromycin, distinct from the extended-release formulation, has recently been developed and has efficacy and tolerability similar to standard immediate-release (IR) clari thromycin, with the advantage of once-daily dosing. Objective: The purpose of this study was to compare the efficacy (as measur ed by relief of clinical symptoms and eradication of specific pathogens) an d tolerability of clarithromycin MR 500 mg administered once daily versus c larithromycin IR 250 mg administered twice daily for 5 days. Methods: In this randomized, double-blind (with matching placebo), parallel -group. multicenter, controlled trial, patients with lower respiratory trac t infection were randomized to 1 of 2 treatment regimens: clarithromycin MR 500 mg once daily plus clarithromycin IR 250 mg placebo twice daily or cla rithromycin IR 250 mg BID plus clarithromycin MR 500 mg placebo once daily. Results: Statistically equivalent clinical cure and success rates, overall symptomatic improvement, and bacteriologic responses were achieved with bot h treatments. In the clarithromycin MR group. the clinical cure rate was 72 .5% (87/120), and the clinical success rate (cure plus symptomatic improvem ent) was 97.5% (117/120). Of the 124 patients treated with clarithromycin I R 250 me BID. 98 (79.0%) achieved a clinical cure, and 120 (96.8%) achieved clinical success. There were no statistically significant between-group di fferences in clinical cure or success rates. More than 85% of patients in b oth study groups experienced improvement in dyspnea, cough, wheezing, chest discomfort, fatigue, and fever, and the visual appearance of sputum; these symptoms resolved completely in the majority of patients. Bacteriologic re sponse (efficacy against specific pathogens), which was assessed as an obje ctive efficacy criterion, was assessable for 40 patients treated with clari thromycin MR and 49 patients treated with clarithromycin IR. Bacteriologic eradication of the pretreatment target pathogen was achieved in 95.0% (38/4 0) of assessable patients treated with clarithromycin MR 500 mg once daily and 91.8% (45/49) of patients treated with clarithromycin IR 250 mg BID. Tr eatment-related adverse events were mild to moderate in all cases. Nausea ( n = 9), diarrhea (n = 6), abdominal pain (n = 5), and gastric pain (n = 3) were the only study drug-related adverse events reported by greater than or equal to1 patient in each treatment arm. Diarrhea was reported only in the clarithromycin IR group (n = 6) (P = 0.029 vs clarithromycin MR). Conclusions: Clarithromycin MR 500 mg administered once daily for 5 days is as effective and well tolerated as the IR formulation, with the advantage of once-daily dosing and fewer episodes of diarrhea.